We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
PD-1 and CTLA-4 exert additive control of effector regulatory T cells at homeostasis.
- Authors
Pereira, Joseph A.; Lanzar, Zachary; Clark, Joseph T.; Hart, Andrew P.; Douglas, Bonnie B.; Shallberg, Lindsey; O'Dea, Keenan; Christian, David A.; Hunter, Christopher A.
- Abstract
At homeostasis, a substantial proportion of Foxp3+ T regulatory cells (Tregs) have an activated phenotype associated with enhanced TCR signals and these effector Treg cells (eTregs) co-express elevated levels of PD-1 and CTLA-4. Short term in vivo blockade of the PD-1 or CTLA-4 pathways results in increased eTreg populations, while combination blockade of both pathways had an additive effect. Mechanistically, combination blockade resulted in a reduction of suppressive phospho-SHP2 Y580 in eTreg cells which was associated with increased proliferation, enhanced production of IL-10, and reduced dendritic cell and macrophage expression of CD80 and MHC-II. Thus, at homeostasis, PD-1 and CTLA-4 function additively to regulate eTreg function and the ability to target these pathways in Treg cells may be useful to modulate inflammation.
- Subjects
REGULATORY T cells; CYTOTOXIC T lymphocyte-associated molecule-4; PROGRAMMED cell death 1 receptors; HOMEOSTASIS; DENDRITIC cells
- Publication
Frontiers in Immunology, 2023, Vol 14, p01
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2023.997376